Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia.
Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia.
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DOI：
10.1016/j.bbrc.2009.01.122
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发表时间：
2009-03
影响因子：
3.1
通讯作者：
Takahiro Yamada;Yoshizumi Takemura;N. Niisato;E. Mitsuyama;Y. Iwasaki;Y. Marunaka
中科院分区：
文献类型：
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作者：
Takahiro Yamada;Yoshizumi Takemura;N. Niisato;E. Mitsuyama;Y. Iwasaki;Y. Marunaka
我们报告了新的N-酰化氨溴索衍生物的影响，（TEI-588 a、TEI-588 b、TEI-589 a、TEI-589 b、TEI-602 a和TEI-602 b：a，芳族胺酰化衍生物; B，脂肪族胺酰化衍生物（一种治疗人类肺部疾病的粘液溶解剂）在Na+/K+/2Cl−协同转运蛋白-1（NKCC 1）作用下对人类粘膜下浆液性Calu-3细胞Cl−分泌的影响。介导的高分泌状态。TEI-589 a、TEI-589 b和TEI-602 a通过降低NKCC 1的活性而不阻断顶端Cl−通道（TEI-589 a>TEI-602 a>TEI-589 b），从而减少Cl−分泌过多，而包括氨溴索在内的任何其他供试化合物对Cl−分泌均无影响。这表明芳香族胺酰化衍生物对Cl−分泌的抑制作用强于脂肪族胺酰化衍生物，并且3-（2，5-二甲基）呋喃甲酰基对Cl−分泌的抑制作用强于环丙酰基。我们在此指出，TEI-589 a、TEI-589 b和TEI-602 a将气道中的高分泌降低至适当水平，提供了该化合物可以通过在高分泌条件下降低气道阻力而成为包括COPD在内的气道阻塞性疾病的有效药物的可能性。
We report the effects of new N-acylated ambroxol derivatives (TEI-588a, TEI-588b, TEI-589a, TEI-589b, TEI-602a and TEI-602b: a, aromatic amine-acylated derivative; b, aliphatic amine-acylated derivative) induced from ambroxol (a mucolytic agent to treat human lung diseases) on Cl−secretion in human submucosal serous Calu-3 cells under a Na+/K+/2Cl−cotransporter-1 (NKCC1)-mediated hyper-secreting condition. TEI-589a, TEI-589b and TEI-602a diminished hyper-secretion of Cl−by diminishing the activity of NKCC1 without blockade of apical Cl−channel (TEI-589a>TEI-602a>TEI-589b), while any other tested compounds including ambroxol had no effects on Cl−secretion. These indicate that the inhibitory action of an aromatic amine-acylated derivative on Cl−secretion is stronger that that of an aliphatic amine-acylated derivative, and that 3-(2,5-dimethyl)furoyl group has a strong action in inhibition of Cl−secretion than cyclopropanoyl group. We here indicate that TEI-589a, TEI-589b and TEI-602a reduce hyper-secretion to an appropriate level in the airway, providing a possibility that the compound can be an effective drug in airway obstructive diseases including COPD by reducing the airway resistance under a hyper-secreting condition.